The Core Reason: A Tale of Isomers and Patents, Not a Ban
The primary reason zopiclone is not available in the United States is rooted in pharmaceutical strategy and regulatory processes, not a safety ban. Zopiclone is a racemic mixture containing two types of molecules called isomers: the (S)-isomer and the (R)-isomer. Research identified that the sleep-promoting effects came mainly from the (S)-isomer.
Sepracor Inc., a pharmaceutical company, isolated and patented this active (S)-isomer, naming it eszopiclone. They pursued and received FDA approval for eszopiclone, which was approved on December 15, 2004, and is sold in the U.S. as Lunesta. This allowed the company to market a patented drug in the U.S. market. Zopiclone itself was never submitted for FDA approval and therefore cannot be legally sold in the U.S.. Both zopiclone and its isomers were classified as Schedule IV controlled substances by the DEA in 2005 due to their potential for abuse.
What is Zopiclone?
Zopiclone is a nonbenzodiazepine hypnotic, part of a group known as "Z-drugs," used for short-term insomnia treatment. It works by increasing the activity of GABA, a brain chemical that has a calming effect. It helps people fall asleep faster and stay asleep longer but is typically recommended for only 2 to 4 weeks to reduce the risk of tolerance and dependence. Zopiclone is available by prescription in many other countries, including Canada, the UK, and Australia.
Eszopiclone (Lunesta): The US-Approved Alternative
Eszopiclone (Lunesta) is the S-isomer of zopiclone and is the prescription medication available in the United States for insomnia. Since it's the active part of zopiclone, its mechanism of action and side effects are very similar. The FDA approved eszopiclone for longer-term use than many other hypnotics at the time, with studies supporting use for up to six months. Common side effects for both drugs include an unpleasant taste, headache, and drowsiness.
Comparison Table: Zopiclone vs. Eszopiclone (Lunesta)
| Feature | Zopiclone | Eszopiclone (Lunesta) |
|---|---|---|
| Legal Status in US | Not commercially available; Schedule IV Controlled Substance | Available by prescription; Schedule IV Controlled Substance |
| FDA Approval | No | Yes (approved Dec. 15, 2004) |
| Chemical Structure | Racemic mixture of (S) and (R) isomers | The single, active (S)-isomer only |
| Common Dosage | 7.5mg (contains 3.75mg of the active S-isomer) | 1mg, 2mg, 3mg |
| Half-Life | ~5-7 hours | ~6-9 hours |
| Common Side Effects | Metallic taste, drowsiness, dry mouth | Unpleasant taste, headache, drowsiness, dry mouth |
| Availability | Generic in many countries (e.g., Canada, UK) | Brand name (Lunesta) and generic in the US |
Potential Risks and Side Effects of Z-Drugs
Z-drugs like zopiclone and eszopiclone carry risks. The FDA requires a boxed warning because of the risk of complex sleep behaviors, such as sleep-driving or making phone calls while not fully awake with no memory of the event.
Other potential risks include:
- Dependence and Withdrawal: Long-term use can lead to dependence. Stopping suddenly can cause withdrawal symptoms.
- Next-Day Impairment: Drowsiness can affect activities like driving the next day.
- Taste Disturbance: A common side effect is a bitter or metallic taste.
- Mental Changes: These drugs can cause abnormal thoughts, anxiety, and worsen depression.
Alternatives to Zopiclone in the United States
Several insomnia treatments are available in the U.S.:
- Eszopiclone (Lunesta): The closest chemical option to zopiclone.
- Other Z-Drugs: Zolpidem (Ambien) and zaleplon (Sonata) are similar nonbenzodiazepine hypnotics.
- Orexin Receptor Antagonists: A newer class including suvorexant (Belsomra).
- Sedating Antidepressants: Low doses of drugs like doxepin (Silenor) or trazodone are sometimes used off-label.
- Benzodiazepines: Medications like temazepam (Restoril) are effective but carry a high risk of dependence.
- Over-the-Counter Options: These include antihistamines like diphenhydramine and supplements like melatonin.
- Non-Pharmacological Approaches: Cognitive Behavioral Therapy for Insomnia (CBT-I) is a recommended first-line treatment.
Conclusion
The absence of zopiclone in the U.S. is a result of pharmaceutical patent strategies rather than a safety issue. It was never approved by the FDA. Instead, its active component, eszopiclone, was developed, patented, and approved. Patients in the U.S. seeking a similar medication can obtain eszopiclone (Lunesta).
